Comparison of diagnostic accuracy of Alzheimer's disease cerebrospinal fluid core biomarkers using INNOTEST, Lumipulse G, and Elecsys assays: Insights from the PUMCH dementia cohort study.

Abstract

BackgroundCerebrospinal fluid (CSF) core biomarkers play a pivotal role in the biological diagnosis of Alzheimer's disease (AD). While various commercial assays and kits are available for quantifying these biomarkers, their performance across diverse clinical settings remains insufficiently evaluated.ObjectiveThis study aimed to compare the diagnostic accuracy of AD core biomarkers using four measurement methods in a Chinese population and to establish method-specific cutoff values tailored to different clinical scenarios.MethodsA total of 309 participants were enrolled from the PUMCH dementia cohort, comprising 176 AD, 114 non-AD dementia cases, and 19 cognitively normal controls (CN). For biomarker quantification, we employed one manual immunoassay (INNOTEST, conducted in two independent laboratories) and two fully automated immunoassay platforms (Lumipulse G and Roche Elecsys). These methods were used to measure CSF Aβ_1-40, Aβ_1-42, t-tau, and p-tau₁₈₁, and to calculate three biomarker ratios (Aβ_1-42/Aβ_1-40, t-tau/Aβ_1-42, and p-tau₁₈₁/Aβ_1-42).ResultsOur findings provide method-specific and clinical context-optimized cutoff values for each application scenario including clinically diagnosed AD versus non-AD dementia, amyloid PET-positive versus PET-negative dementia, and AD versus CN. The accuracy of differential diagnosis was higher using biomarker ratios (Aβ_1-42/Aβ_1-40, t-tau/Aβ_1-42, p-tau₁₈₁/Aβ_1-42) than absolute values. Most of the high accuracy was achieved using automated assays especially Lumipulse G rather than manual assays.ConclusionsIn this first comparative study of three immunoassays in a Chinese cohort, automated assays demonstrated superior performance compared to manual assays. We established assay-specific cutoff values tailored to different clinical contexts in a Chinese population.